Antibody detection in patients with invasive aspergillosis

The clinical significance of Aspergillus antibody assays for the diagnosis of invasive aspergillosis (IA) is unclear. In two studies, three different antibody assays were evaluated with patients suffering from proven IA: (i) a commercial haemagglutination test (HAT), (ii) a commercial enzyme immunoassay (EIA) for IgG, IgM, and IgA, and (iii) an experimental mitogillin enzyme immunoassay for IgG, IgM, and IgA. In the first study, 99 serum samples from 26 patients with IA and 22 serum samples from 22 control patients were tested with all the three tests. Ten of the 26 patients (38%) reacted positively in at least one antibody assay. The highest sensitivity was generated by the detection of IgG using the EIA formats (22 and 21%, respectively), the HAT had a sensitivity of 8%. IgM type antibodies were detected in only two patients; no IgA type antibodies were detected. The specificities of the IgG EIA and the HAT were 72 and 85%, respectively. Antibody detection was the single positive laboratory test in two patients with proven and probable IA. In the second study, antibody test results of 60 patients with proven IA were retrospectively evaluated. Fourteen patients (23%) tested positive in the EIA and/or in the HAT. Investigations of the antibody levels in individual immunocompromised patients over time revealed that IgG production started after a mean of 10.8 days after diagnosis of IA. To conclude, antibodies against Aspergillus were detected in 23% of patients with IA. The antibody production started in successfully treated immunosuppressed patients after a mean of 10.8 days after the onset of infection. In particular, the detection of IgG-antibodies with an EIA can be useful for the confirmation of the diagnosis of IA and for the monitoring of the treatment of IA.     

Serum neuron-specific enolase is a useful tumor marker for small cell lung cancer

Small cell lung cancer (SCLC) may be potentially curable. A correct diagnosis of cancer cell type is important and serum markers are of great value. Although several markers have been suggested, they have been of limited value because of insufficient specificity. To assess the value of serum neuron-specific enolase (S-NSE) as a possible marker of SCLC, the serum levels of 81 patients with SCLC (59 patients with extensive disease and 22 patients with limited disease) were compared with the serum levels of patients with non-small cell lung cancer (N-SCLC) and 93 patients with nonmalignant lung diseases. The S-NSE level also was measured in 104 patients with extensive disease of various other malignancies, including 71 solid tumors and 33 malignant hematologic disorders. From 105 healthy control subjects, the upper limit of the normal range (x + 2 standard deviations [SD]) was determined as 12.3 ng/ml. The S-NSE level was elevated in 78% of patients with SCLC, including 11 of 22 (50%) with limited disease and 52 of 59 (88%) with extensive disease. In contrast, the S-NSE level was raised only in 18% of patients with advanced N-SCLC (nine of 50) and 6% of patients with nonmalignant lung diseases (six of 93). Twelve patients (17%) with other solid malignant tumors and two patients (6%) with malignant hematologic disorders had raised S-NSE levels. Serial N-NSE levels were obtained in 13 patients with SCLC. S-NSE levels fell in all patients responding to chemotherapy and increased again with progression of disease. Our results indicate that S-NSE seems to be specific for SCLC (85%), whereas sensitivity seems to be dependent on the stage of disease. Further, S-NSE may be a useful marker for monitoring treatment and predicting relapse in patients with SCLC.     

Sensitivity of galactomannan enzyme immunoassay for diagnosing breakthrough invasive aspergillosis under antifungal prophylaxis and empirical therapy

Data on diagnostic performance of Galactomannan (GM) testing in patients under mould‐active regimens are limited. Whether sensitivity of GM testing for diagnosing breakthrough invasive aspergillosis (IA) is decreased under antifungal prophylaxis/therapy remains therefore a point of discussion. We retrospectively analysed GM test results in patients who were admitted with underlying haematological malignancies to two Divisions of the Medical University Hospital of Graz, Austria, between 2009 and 2012. Only cases of probable and proven IA that were diagnosed by other methods than GM testing were included (time of diagnosis = day 0). We compared GM results of patients with/without therapy/prophylaxis for the period of 2 weeks prior (week ?2) until 3 weeks postdiagnosis. A total of 76 GM test results in nine patients were identified. Six patients had received antifungal therapy/prophylaxis from week ?2, whereas three patients were treated with therapy from the time of diagnosis at week 0. GM testing was positive in 45/76 (59%) of samples. Sensitivity of GM testing for detection of proven or probable IA at week ?1 and 0 was 77% and 79% in patients with mould‐active regimens. We conclude that GM testing might be a useful diagnostic method for breakthrough IA in patients receiving mould‐active prophylaxis/therapy.     

晚期肺鳞癌患者肿瘤标志物测定的临床分析

背景与目的肺鳞癌由于发病隐匿,早期无明显症状,往往到晚期才得以诊断。本研究旨在描述性分析晚期肺鳞癌患者的基本特征和多种肿瘤标志物检测水平及阳性率情况,评价其临床价值。方法以2011年1月-2015年12月期间于中国医学科学院肿瘤医院诊治的晚期肺鳞癌患者作为研究对象,通过病历回顾收集相关资料,描述性分析晚期肺鳞癌患者基本特征、肿瘤标志物检测水平和阳性率。结果260例患者的平均年龄为（59.4±9.2）岁,男性223例（85.8%）,女性37例（14.2%）。203例（78.1%）有吸烟史,8例（3.1%）有癌症家族史。细胞角质蛋白19的片断（cytokerantin 19 fragment, CYFRA21-1）的检测阳性率最高（71.2%）。不同肿瘤原发灶（tumor, T）分期和淋巴结受累（node, N）分期患者五种指标检测水平无统计学差异（P>0.05）,仅鳞状细胞癌相关抗原（squamous cell carcinoma antigen, SCC）在不同T分期的检测阳性率有统计学差异（P=0.035）。二联阳性率最高的为CYFAR21-1+蛋白质类的癌胚抗原（carcinogen-embryonic antigen, CEA）,阳性率为82.7%,三联阳性率最高的为癌抗原12-5（cancer antigen 125, CA125）+CYFAR21-1+CEA,阳性率为84.6%,四联阳性率最高为CA125+CYFAR21-1+CEA+酶类标志物神经烯醇化酶（neuron speciifc enolase, NSE）,阳性率为85.0%,五联的阳性率为86.2%。结论 CYFAR21-1的检测阳性率最高,单项肿瘤标志物的检测灵敏度较低,联合检测可提高对肺鳞癌的诊断灵敏度,首选CA125、CYFAR21-1和CEA联合。     

F-18]Fluorodeoxyglucose positron emission tomography can predict pathological tumor stage and proliferative activity determined by Ki-67 in clinical stage IA lung adenocarcinomas

OBJECTIVE: To predict a malignant grade of lung cancer by fluorodeoxyglucose positron emission tomography (FDG-PET) scanning, we investigated the correlation between FDG uptake and pathological tumor stage, proliferative activities determined by Ki-67 and cyclin D1, and an alteration of p53, in clinical stage (c-stage) IA lung adenocarcinomas. METHODS: FDG-PET was performed for 71 patients with c-stage IA lung adenocarcinomas. FDG uptake was measured by a contrast ratio (CR) between the tumor and contralateral lung. Ki-67, cyclin D1 and p53 staining scores were examined by immunohistochemistry. RESULTS: The lesions with ground-glass opacity were found in 26 patients, and solid lesions in 45 by computed tomography. The pathological tumor stages (p-stage) were stage IA in 59 and more advanced stages in 12. The latter had significantly higher CR value than the former (P < 0.001). Patients with CR > or = 0.55 could be predicted to be at advanced tumor stages, with a sensitivity of 0.83 and a specificity of 0.82. The CR and staining scores of Ki-67 were significantly correlated with each other (P < 0.0001), and both the values were significantly higher in advanced tumor stages than in p-stage IA, and were also significantly higher in tumors with intratumoral lymphatic, vascular and pleural involvements than in those without such features (P < 0.05-0.0001). CONCLUSIONS: In c-stage IA lung adenocarcinomas, the FDG uptake can predict p-stage and tumor proliferative activity determined by Ki-67. For c-stage IA lung adenocarcinomas showing CR > or = 0.55, mediastinoscopy or neoadjuvant chemotherapy is indicated.     

Aberrant methylation of the adenomatous polyposis coli promoter 1A in bronchial aspirates from patients with suspected lung cancer

Promoter hypermethylation is a major mechanism for gene silencing and offers a promising starting point for developing molecular biomarkers. The purpose of our study was to determine aberrant methylation of the adenomatous polyposis coli (APC) gene promoter 1A with respect to its prevalence and quantitative level in bronchial aspirates from patients with suspected lung cancer. Applying quantitative methylation-specific PCR, 155 bronchial aspirates from patients with non-small cell cancer (NSCLC) and small cell cancer (SCLC) of the lung as well as 67 bronchial aspirates from patients diagnosed for nonneoplastic lung disease were examined in a retrospective case-control study. Aberrant APC promoter 1A methylation was seen in 71% of NSCLCs, 38% of SCLCs and 42% of patients with nonneoplastic lung disease, being therefore not specific for the presence of primary lung cancer. In contrast, quantitative analysis showed a significantly higher methylation level of bronchial aspirates from NSCLC as compared to patients without neoplastic lung disease. Introducing a cutoff point that defined high level of APC hypermethylation NSCLC could be discriminated from cases without neoplastic disease with a specificity of 98.5% and a sensitivity of 39%. The data suggest that quantitative analysis of APC hypermethylation may serve as a biomarker of primary lung cancer.     

Results of conservative treatment in epithelial ovarian carcinoma.

BACKGROUND: The objective of this study was to assess and evaluate the clinical outcome and fertility in patients treated conservatively for epithelial ovarian carcinoma (EOC). METHODS: Thirty-one patients treated with conservative management EOC were followed up. Optimal surgical staging was performed in 2 cases during the initial surgery and in 27 patients during a reassessment surgery. Six patients underwent hysterectomy during this restaging surgery. RESULTS: Among 25 patients treated conservatively after the restaging surgery, the International Federation of Gynecology and Obstetrics (FIGO) staging distribution was 19 Stage IA (Grade 1, n = 9; Grade 2, n = 10), 1 Stage IC, 2 Stage II, and 3 patients with initial stage unknown. Seven patients had recurrence (five on the remaining ovary). The disease free survival rate at 5 years for patients with Stage IA Grade 1 and 2 tumors were 89% and 71%, respectively. All patients with Stage IA or higher disease experienced recurrence. Only four pregnancies (three spontaneous and one after in vitro fertilization procedure) were obtained. CONCLUSIONS: Conservative surgery for patients with EOC could be considered in young patients with Stage IA Grade 1 disease adequately staged and desiring to preserve fertility potential. This procedure should not performed in patients with disease staged higher than FIGO Stage IA.     

Invasive aspergillosis in a paediatric haematology department: a 15-year review

Invasive aspergillosis (IA) is an increasingly common and often fatal fungal infection in children with haematological disorders. To describe the epidemiology, diagnosis, treatment and outcome of IA in children, retrospective review of the medical records of proven and probable IA between January 1986 and December 2000 was used. Twenty-four patients with IA were identified (10 proven and 14 probable) with a median age of 8.5 years. The incidence of IA was particularly high in acute myeloblastic leukaemia (5.35%) and leukaemia relapse (4%). Twenty-two patients presented with lung involvement. Broncho-alveolar lavage led to a diagnosis in 11 cases, but diagnosis was difficult and repeated invasive explorations were required. Antifungal therapy mainly consisted of amphotericin B. Eight patients underwent open-thorax surgery without any complication. Nine patients (37.5%) were cured of IA and three are still alive. The mortality was 87.5%. Three patients died of massive haemoptysis, including two before neutropenia recovery. Four patients presented with IA recurrence and three were cured again. Despite significant progress having been made in the treatment and diagnosis of IA, it is still a devastating complication in children with haematological disorders. New antifungal therapies and strategies are promising, but objective data are still lacking.     

Clinical characteristics of 45 patients with invasive pulmonary aspergillosis

BACKGROUND:

Invasive aspergillosis (IA) is a common complication in patients with hematologic malignancies. Patients with solid tumors also are at risk for IA because they may develop neutropenia as a result of chemotherapy and radiotherapy. However, studies of IA in patients with solid tumors are rare. In this study, the risk factors and clinical characteristics of pulmonary infection and death mediated by invasive pulmonary aspergillosis (IPA) as complications in patients with lung cancer were determined.

METHODS:

The authors conducted a retrospective analysis of the clinical notes from 45 patients who had IPA.

RESULTS:

Among 1711 patients with lung cancer, 45 patients contracted pulmonary aspergillosis (2.63%). There were 10 cases of proven disease and 35 cases of probable disease. In univariate analysis, the main predisposing factors were clinical stage IV disease (P = .018), chemotherapy during the month preceding infection (P = .033), and corticosteroid use (≥3 days; P = .038). In multivariate analysis, only clinical stage IV disease (P = .018) was associated with IPA. Furthermore, the mortality rate among lung cancer patients who had pulmonary aspergillosis was 51.1% (23 of 45 patients). Of the patients who died, corticosteroid therapy (P = .001) and grade 3/4 neutropenia (P = .013) were correlated statistically with pulmonary aspergillosis in patients with lung cancer.

CONCLUSIONS:

In univariate analysis, the risk factors for IPA in lung cancer included chemotherapy and corticosteroid use in the month preceding infection and clinical stage IV disease. However, in multivariate analysis, only clinical stage IV disease was identified as a risk factor for IPA. Cancer 2009. © 2009 American Cancer Society.     

Pattern of disease recurrence and prognostic factors in patients with osteosarcoma treated with contemporary chemotherapy

BACKGROUND: The goal of the current study was to define the clinical features and outcome of recurrent osteosarcoma (OS) in children and young adults initially treated with contemporary chemotherapy. METHODS: The authors reviewed the clinical features, therapy, and outcome for 59 patients from the Mayo Clinic (Rochester, MN) and Children's Hospital and Regional Medical Center (Seattle, WA). They were diagnosed initially with OS between January 1990 and December 2000, received multiagent chemotherapy (most frequently cisplatin, doxorubicin, high-dose methotrexate, and ifosfamide), and developed disease recurrence after achieving an initial complete response (CR). RESULTS: The most common site of initial disease recurrence was the lung only (n = 36 patients), followed by distant bone (n =8 patients), combined lung and other sites (n =7 patients), and other sites (n =8 patients). The median time to first disease recurrence was 15 months (range, 2-92 months) from the initial diagnosis. Thirty patients with isolated pulmonary recurrence achieved a second CR, either with surgery alone (n =15 patients) or surgery and salvage chemotherapy (n =15 patients). For this group, the 4-year disease-free survival (DFS) and overall survival rates were 7% (95% confidence interval [95% CI], 0-16%) and 28% (95% CI, 11-45%), respectively. For all 59 patients with recurrent OS, the 4-year DFS and overall survival rates were 6% (95% CI, 0-12%) and 23% (95% CI, 10-36%), respectively. The only factors associated with improved DFS and overall survival rates were unilateral pulmonary recurrence, solitary pulmonary nodule at recurrence, more than 24 months between the initial diagnosis and first disease recurrence, and achievement of a second CR. CONCLUSIONS: The DFS and overall survival rates for recurrent OS after contemporary therapy remained poor even for patients with isolated pulmonary recurrence. Therefore, new treatment strategies are needed.     

Therapy of invasive aspergillosis with itraconazole: improvement of therapeutic efficacy by early diagnosis

We report on the treatment of invasive aspergillosis with the new triazole antimycotic agent itraconazole. All 11 patients suffered from pulmonary invasive aspergillosis. Two patients also had cerebral aspergillosis; in one of these patients the paranasal sinuses were also invaded. Underlying diseases were acute lymphoblastic leukaemia (n = 3), acute myeloid leukaemia (n = 4); one patient underwent allogeneic bone marrow transplantation before he developed aspergillosis; another was transplanted after successful aspergillosis treatment, liver cirrhosis (n = 1), lung infarction after pulmonary embolism (n = 1), chronic bronchitis after pulmonary tuberculosis (n = 1) and AIDS (n = 1). In five cases initial diagnosis was established by means of mycological methods and clinical signs. In six patients invasive pulmonary aspergillosis was initially diagnosed due to the clinical criteria presented in this paper. Secondary mycological confirmation after onset of therapy was achieved in five out of these six patients. All of the patients initially responded to therapy. One female patient experienced a relapse of aspergillosis and died of cerebral involvement and relapsing leukaemia. Two further patients died due to underlying diseases (pulmonary embolism, relapsing leukaemia). Nine patients (82%) were cured of the mycosis, including the patient with cerebral involvement; two underwent surgical resection of residual pulmonary lesions. Itraconazole is a very effective drug for treatment of invasive aspergillosis. Therapeutic efficacy can be optimized by early diagnosis using clinical criteria and prompt start of treatment.     

An evaluation of ovarian carcinoma-associated antigen defined by murine monoclonal antibody CF511 in sera from patients with ovarian carcinoma

Murine monoclonal antibody CF511, raised against human ovarian clear cell carcinoma, detects a glycoprotein (Mr 600 kDa) called CF511 antigen which is elevated in the serum of many patients with ovarian carcinoma. A competitive enzyme-linked immunosorbent assay was developed to detect CF511 antigen in human serum and used to detected CF511 antigen in subjects with ovarian carcinoma and other diseases. No raised levels (less than 18 unit (U) ml-1) of the antigen were found in the serum of 220 normal individuals or of patients with germ cell tumours (n = 6), granulosa theca cell tumour (n = 1), gastric carcinomas (n = 10) and colo-rectal carcinomas (n = 8). Raised serum levels of CF511 antigen were found in 6/46 patients (13.0%) with benign gynaecological tumours (including endometriosis or ovarian cyst), in 5/7 patients (71.4%) with breast carcinoma and 16/21 (76.2%) lung carcinoma patients. In patients with ovarian carcinoma, 42.3% (11/26) of stage I and II, and 96.0% (24/25) of stage III and IV had levels of greater than or equal to 18 U ml-1. In all patients with serial determination of CF511 antigen levels before and after the surgery, the levels of antigen correlated with the clinical course of disease. Determination of CF511 antigen levels may be useful for detection of ovarian carcinoma as well as lung and breast carcinomas and for monitoring progress of disease and response to therapy.     

大剂量三苯氧胺逆转对EP方案耐药的非小细胞肺癌

目的：研究大剂量三苯氧胺（tamoxifen,TAM)逆转治疗对鬼臼乙叉甙－顺铂（EP）方案耐药，且P－gp表达阳性的非小细胞肺癌。方法：41例对EP方案耐药，且P－gp阳性的NSCLC患者随机分为二组，逆转组应用TAM100mg,2次／日，每1－5天，然后采用EP方案，对照组仅采用EP方案治疗.结果：逆转组CR1例，PR5例，NC11例，PD4例，有效率为28．6％（6／21），中位生存期为8．4月，1年生存率为38．1％，对照组NC9例，PD11例，有效率为0，中位生存期为4．6月，1年生存率为35．0％，逆转组有效率明显高于对照组（P＝0．0121），中位生存期明显长于对照组（P＜0．01）。逆转 P－gp阴转率为33．3％（7／21），对照组无阴转者，主要毒副反应为Ⅱ-Ⅲ度血液学毒性，Ⅳ度少见，消化道反应均为Ⅰ－Ⅱ度。两组间毒副反应比较均无显著差异（P＞0．05）。结论：大剂量三苯氧胺能逆转对EP方案耐药，且P－gp表达阳必的非小细胞肺癌。     

Results of a prospective trial of mantle irradiation alone for selected patients with early-stage Hodgkin's disease.

PURPOSE: To determine the efficacy of mantle radiation therapy alone in selected patients with early-stage Hodgkin's disease. PATIENTS AND METHODS: Between October 1988 and June 2000, 87 selected patients with pathologic stage (PS) IA to IIA or clinical stage (CS) IA Hodgkin's disease were entered onto a single-arm prospective trial of treatment with mantle irradiation alone. Eighty-three of 87 patients had > or = 1 year of follow-up after completion of mantle irradiation and were included for analysis in this study. Thirty-seven patients had PS IA, 40 had PS IIA, and six had CS IA disease. Histologic distribution was as follows: nodular sclerosis (n = 64), lymphocyte predominant (n = 15), mixed cellularity (n = 3), and unclassified (n = 1). Median follow-up time was 61 months. RESULTS: The 5-year actuarial rates of freedom from treatment failure (FFTF) and overall survival were 86% and 100%, respectively. Eleven of 83 patients relapsed at a median time of 27 months. Nine of the 11 relapses contained at least a component below the diaphragm. All 11 patients who developed recurrent disease were alive without evidence of Hodgkin's disease at the time of last follow-up. The 5-year FFTF in the 43 stage I patients was 92% compared with 78% in the 40 stage II patients (P =.04). Significant differences in FFTF were not seen by histology (P =.26) or by European Organization for Research and Treatment of Cancer H-5F eligibility (P =.25). CONCLUSION: Mantle irradiation alone in selected patients with early-stage Hodgkin's disease is associated with disease control rates comparable to those seen with extended field irradiation. The FFTF is especially favorable among stage I patients.     

A randomized prospective multicentre trial of cefpirome versus piperacillin-tazobactam in febrile neutropenia.

Fever is frequently the only clinical sign of infection in patients with chemo-induced neutropenia. In this setting, empirical administration of broad spectrum antibiotics must be rapid. The aim of this work was to compare, for the first time, cefpirome (CPO) and piperacillin-tazobactam (PT) in a large randomized trial. Two hundred-eight febrile neutropenic episodes (FNE) (> or = 38.5 degrees C and ANC < or = 0.5 giga/l) were treated by randomization, as first line therapy, using either CPO 2 g x 2/day (105 cases) or PT 4 g x 3/day (103 cases), alone (CPO: 15/PT: 15), or plus aminoglycoside (165 cases, CPO: 82/PT: 83) or quinolone (CPO: 2/PT: 2). There were 131 men and 77 women aged between 17 and 83 years (median: 49) who received chemotherapy (n = 160) or allogeneic (n = 10) or autologous (n = 38) stem cell transplantations. Underlying diseases were: acute leukemia (n = 131), lymphoma (n = 33), myeloma (n = 16), solid tumor (n = 8), myeloproliferative disorder (n = 9), chronic lymphoid leukemia (n = 5), aplastic anemia (n = 3), myelodysplasia (n = 3). Distribution of age, neutropenia duration (median: 17 days), underlying disease, and protocol therapy duration (median: 11 days) was comparable in both arms. A microbiologically documented infection (MDI) was evidenced in 57 cases (27%). Bacteria were isolated from blood cultures in 54 cases (Gram positive: 32 cases). Their in vitro susceptibility rates to CPO and PT were not different. Two days after antibiotics initiation, clinical (fever disappearance) and microbiological (culture negativation) success rates (SR) were 62% for CPO versus 61% for PT and 50% versus 55% respectively in case of MDI (p = 0.89). Two deaths and 77 failures were registered. At the end of protocol, SR (no antibiotic change/absence of superinfection) was 59% with CPO versus 50% with PT (p = 0.27) and 53% versus 40% respectively in the 151 cases with neutropenia > or = 10 days (p = 0.17). The occurrence of side effects was similar in both arms. In our hands, the efficacy of CPO and PT was comparable for treating FNE.     

Preoperative cytodiagnosis of very small-sized peripheral-type primary lung cancer

To demonstrate the importance of preoperative diagnosis of pulmonary cancers presenting as peripheral small-sized solitary shadows we evaluated the results of morphologic definitive diagnosis together with various clinical factors in 91 tumors with less than 15-mm diameter resected surgically between 1983 and 1999. Histologically, these tumors consisted of 73 adenocarcinomas, nine squamous cell carcinomas, and nine other types. Regarding the pathologic stage, 57 tumors were classified in stage IA, three in IB, six in IIA, seven in IIIA, 14 in IIIB, and four in IV. Comparing various biopsy techniques, the sensitivity of preoperative cytodiagnosis was 43.7% for transbronchial brushing (n = 48), 52.9% for transbronchial forceps biopsy-stamp cytology (n = 51), 66.6% for transbronchial fine needle aspiration (n = 78), and 85.0% for percutaneous fine needle aspiration (n = 20). The overall sensitivity of preoperative cytodiagnosis was 79.0% for transbronchial biopsy (n = 81), and 87.3% for transbronchial and percutaneous biopsy (n = 87). Of 73 clinical N0 cases in which lobectomy was performed, 10 cases (13.6%) were diagnosed as between pathological degrees N1, N2 and N3. However, lung cancer cases with less than 10-mm diameter did not have lymph node metastasis. Our study of histologic differentiation showed that all cases of well-differentiated adenocarcinomas (n = 20) were pathological degree N0. The overall sensitivity of preoperative diagnosis increased to 89.1% in cases (n = 74) of tumors with 11-15-mm diameter. The sensitivity of cytodiagnosis for peripheral small-sized primary lung cancers is high, and we can estimate histological differentiation based on the cytological findings. Therefore, cytodiagnosis is an effective and indispensable diagnostic method for determination of the optimal treatment approach, including approaches such as intentionally limited resection.     

五种肿瘤标志物联检在小细胞肺癌诊断中的价值

目的:探讨五种肿瘤标志物［癌胚抗原（CEA）、神经元特异性烯醇化酶（NSE）、细胞角蛋白19片段（Cyfra21-1）、胃泌素释放肽前体（ProGRP）、人附睾蛋白4（HE4）］联合检测在不同分期小细胞肺癌诊断中的价值。方法:应用电化学发光法分别检测117例小细胞肺癌患者（Ⅰ期23例、Ⅱ期26例、Ⅲ期39例、Ⅳ期29例）,70例肺部良性疾病患者及120名健康体检者血清中CEA、NSE、Cyfra21-1、ProGRP和HE4水平。结果:小细胞肺癌组五种肿瘤标志物水平均高于健康对照组和肺部良性病变组,差异有统计学意义（P＜0.05）;血清ProGRP浓度随疾病进展而明显升高,其表达水平与临床分期密切相关（P＜0.05）。血清HE4表达水平Ⅱ期高于Ⅰ期,Ⅳ期高于Ⅲ期,差异有统计学意义（P＜0.05）;五种肿瘤标志物联合检测诊断小细胞肺癌的效能最高,各单项指标诊断效能由高到低依次为AUCProGRP 0.91>AUCHE4 0.89>AUCNSE 0.80>AUCCyfra21-1 0.64>AUCCEA 0.60。结论:血清ProGRP是诊断不同分期SCLC良好的肿瘤标志物,在SCLC早期也具有较高的灵敏度和特异度,血清HE4和NSE是较好的补充,多肿瘤标志物联合检测仍是提高诊断效能的最佳选择。     

Five-year-survey of invasive aspergillosis in a paediatric cancer centre. Epidemiology, management and long-term survival.

The epidemiology, management, and long-term survival of invasive aspergillosis was assessed in a prospective, 5-year observational study in 346 unselected paediatric cancer patients receiving dose-intensive chemotherapy for newly diagnosed or recurrent malignancies. Invasive aspergillosis occurred exclusively in the context of haematological malignancies, where it accounted for an incidence of 6.8% (n = 13 of 189). The lung was the primary site in 12 cases, and dissemination was present in three of those. Prior to diagnosis, the overwhelming majority of patients had been profoundly neutropenic for at least 14 days (n = 11 of 13) and were receiving systemic antifungal agents (n = 10 of 13). Clinical signs and symptoms were nonspecific but always included fever. All 11 patients who were diagnosed and treated during lifetime for a minimum of 10 days responded to either medical or combined medical and surgical treatment, and seven were cured (64%). Nevertheless, the overall long-term survival was merely 31% after a median follow-up of 5.68 years after diagnosis. Apart from refractory or recurrent cancer, the main obstacles to successful outcome were failure to diagnose IA during lifetime and bleeding complications in patients with established diagnosis. The frequency of invasive aspergillosis of greater than 15% in paediatric patients with acute myeloblastic leukaemia and recurrent leukaemias warrants the systematic investigation of preventive strategies in these highly vulnerable subgroups.     

Regional chemotherapy for hepatic metastases of colorectal carcinoma (continuous intraarterial versus continuous intraarterial/intravenous therapy). Results of a controlled clinical trial

Sixty-four patients with a biopsy diagnosis of colorectal cancer with liver metastases were treated with 5-fluorodeoxyuridine (FUDR) infusions. In a pilot study, the first 20 patients were given hepatic artery infusions of FUDR by implanted pumps. The remaining 44 patients were then randomized prospectively to compare the effectiveness of continuous hepatic artery and intravenous infusion of FUDR (IA/IV group; 21 patients) with hepatic artery infusion alone (IA group; 23 patients). A continuous 14-day infusion regimen of FUDR was applied each month. The dosage was 0.2 mg/kg/d of FUDR for the IA group and 0.3 mg/kg/d for the IA/IV group. The complete and partial response rates were each 50% in the pilot study and 52% and 48% in the IA and IA/IV randomized groups, respectively. Drug toxicities in the 64 patients included gastroenteritis (21%), chemical hepatitis (57%), and biliary sclerosis (25%). There was no difference in the toxicity of FUDR in the two randomized groups (P greater than 0.1). Extrahepatic spread of cancer during therapy was found in 61% (n = 14) of the IA group and 33% (n = 7) of the IA/IV group. There was no difference in survival between the randomized groups. The 64 patients were categorized into the following two groups according to their response to therapy: (1) responders (patients with complete or partial remission [n = 32]) or nonresponders (patients with stable disease or progression of metastases [n = 32]). The median survival time was 31 months for responders and 16 months for nonresponders (P less than 0.0001). Intraarterial FUDR infusion provided control of liver metastases. The combination of intraarterial and intravenous therapy seemed to prevent extrahepatic spread during therapy in most of the patients. Survival appeared to be significantly prolonged in patients with a regression of metastases.     

Analysis of treatment modalities and prognosis on microinvasive cervical cancer: a 10-year cohort study in China

Objective

To explore appropriate treatment modality of microinvasive cervical cancer (MIC) and to analyze prognosis and risk factors of recurrence.

Methods

A cohort of 324 Chinese patients with MIC diagnosed and treated at Peking Union Medical College Hospital was retrospectively reviewed. Demographic features, treatment modalities, pathologic parameters, risk factors of residual disease, survival and risk factors of recurrence were analyzed.

Results

Of all patients, 280 cases were staged IA1 and 44 cases staged IA2 MIC. Twenty-five cases (7.7%) were found to have lympho-vascular space involvement (LVSI), but no parametrial involvement or ovarian metastasis was detected. Only one staged IA2 patient with LVSI was found to have lymph node metastasis. 32.4% patients (82/253) had residual diseases after conization. No significant difference of LVSI, lymph node metastasis and residual disease after coniztion was found between stage IA1 and IA2 MIC patients. Multivariate logistic analysis showed positive margin was the only independent risk factor of residual disease after conization (odds ratio [OR], 4.18; p<0.001). Recurrence occurred in five cases, but no mortality was found. Progression-free survival for stage IA1 patients treated by conization or hysterectomy was similar (92.3% and 98.8%, p=0.07). Cox regression analysis revealed LVSI as an independent risk factor for recurrence in stage IA1 patients (OR, 12.14; p=0.01).

Conclusion

For stage IA1 patients with negative resection margin and no LVSI, conization can be an ideal treatment modality. For stage IA2 patients, more conservative surgery such as simple hysterectomy may be considered. LVSI is an independent risk factor for recurrence in patients with stage IA1 cervical cancer.